The present investigation was undertaken to study the association between placental apoptosis and pre-eclampsia, discriminating between pre-eclamptic pregnancies with appropriate-, and small-for-gestational-age (SGA), infants. Twenty pregnancies with pre-eclampsia and SGA (birth weight at or below -2 standard deviations) infants were selected in a retrospective study. Subsequently, corresponding numbers of gestational age-matched pre-eclampsia cases with appropriate-gestational-age (AGA) (birth weight at or above the 50% centile) infants and AGA controls without pre-eclampsia were selected. Formalin-fixed placental tissue was obtained from all groups. Apoptosis was assessed by a monoclonal antibody (M30), detecting a neoepitope of cytokeratin that is generated early in the apoptotic cascade. M30-positive cells were counted in villous and decidual/ basal plate tissue fields, and results were given as numbers of M30-positive cells per field. The study was performed blinded. Increased apoptosis was found in the syncytiotrophoblast layer in pre-eclampsia with SGA infants (0.14 apototic incidents per field of villous tissue, with 0.04-0.23 as the corresponding 25-75% inter quartile range (IQR) (P=0.05)). Syncytial apoptosis in the syncytial layer in the pre-eclampsia group with AGA infants was lower (0.09, IQR 0.03-0.15) and corresponded to the level detected among controls (0.06, IQR 0.03-0.17). Apoptosis in other placental cellular compartments did not differ between groups. The increased syncytial apoptosis found in placentas from pregnancies with SGA infants may either be due to specific mechanisms associated with pre-eclampsia complicated with growth restriction, or may simply reflect the presence of syncytiotrophoblast layer damage, regardless of underlying pathological condition.